Objective: Structural alterations of small resistance arteries in essential hypertensive patients (EH) are mostly characterized by inward eutrophic remodeling. However, we observed hypertrophic remodeling in patients with renovascular hypertension, in those with acromegaly, as well as in patients with non-insulin-dependent diabetes mellitus, suggesting a relevant effect of humoral growth factors on vascular structure, even independent from the hemodynamic load. Cortisol may stimulate the renin-angiotensin system and may induce cardiac hypertrophy. However, presently no data are available about small artery structure in patients with Cushing's syndrome.

Subjects: We have investigated the structure of sc small resistance arteries in 12 normotensive subjects (NT), in 12 EH subjects, and in eight patients with Cushing's syndrome (CS). Small arteries from sc fat were dissected and mounted on a micromyograph. The normalized internal diameter, media thickness, media to lumen ratio, and the media cross-sectional area were measured, as well as indices of oxidative stress.

Results: Demographic variables were similar in the three groups, except for clinic blood pressure. The media to lumen ratio was significantly greater in EH and CS, compared with NT; no difference was observed between EH and CS. The media cross-sectional area was significantly greater in CS compared with EH and with NT. An increased vascular oxidative stress was present in CS, as demonstrated by increased levels of superoxide anions, cyclooxygenase-1 and endothelial nitric oxide synthase in the microvessels.

Objective: The aim of the study was to evaluate a 35-yr-old woman with ACTH-independent hypercortisolism associated with both micronodular adrenal hyperplasia and ectopic pararenal adrenocortical adenoma.

Design and Setting: In vivo and in vitro studies were performed in a University Hospital Department and academic research laboratories.

Intervention: Mutations of the PRKAR1A, PDE8B, and PDE11A genes were searched for in leukocytes and adrenocortical tissues. The ability of adrenal and adenoma tissues to synthesize cortisol was investigated by immunohistochemistry, quantitative PCR, and/or cell culture studies.

Main Outcome Measure: Detection of 17{alpha}-hydroxylase and 21-hydroxylase immunoreactivities, quantification of CYP11B1 mRNA in adrenal and adenoma tissues, and measurement of cortisol levels in supernatants by radioimmunological assays were the main outcomes.

Results: Histological examination of the adrenals revealed nonpigmented micronodular cortical hyperplasia associated with relative atrophy of internodular cortex. No genomic and/or somatic adrenal mutations of the PRKAR1A, PDE8B, and PDE11A genes were detected. 17{alpha}-Hydroxylase and 21-hydroxylase immunoreactivities as well as CYP11B1 mRNA were detected in adrenal and adenoma tissues. ACTH and dexamethasone activated cortisol secretion from adenoma cells. The stimulatory action of dexamethasone was mediated by a nongenomic effect involving the protein kinase A pathway.

Wednesday, November 25, 2009

MaryO’Note: This is a political article which may or may not be of interest to readers but the “dissenting journalist” has Cushing’s.

…Taoufik Ben Brik, who suffers from diabetes and a rare hormonal disorder called Cushing's Syndrome, for which he needs regular medication, appeared physically weak and was unable to stand throughout the proceedings…

Read it at http://www.amnesty.org/en/news-and-updates/news/tunisian-authorities-must-release-dissenting-journalist-20091124

Objective: In patients with active Cushing’s Syndrome (CS), cardiac structural and functional changes have been described in a limited number of patients. It is unknown whether these changes reverse after successful treatment. We therefore evaluated the changes in cardiac structure and dysfunction after successful treatment of CS, using more sensitive echocardiographic parameters (based on 2-dimensional strain imaging) to detect subtle changes in cardiac structure and function.

* To whom correspondence should be addressed. E-mail: philippe.chanson@bct.aphp.fr.

Context and Objective: Metabolic and body compositional consequences of GH deficiency (GHD) in adults are associated with a phenotype similar to the metabolic syndrome (MetS).

Patients: We assessed MetS prevalence in adult GHD patients (n = 2531) enrolled in the Hypopituitary Control and Complications Study. Prevalence was assessed at baseline and after 3 yr of GH replacement in a subset of 346 adult-onset patients.

Conclusion: MetS prevalence in GHD patients was higher than in the general population in the United States and higher in the United States than Europe. Prevalence was unaffected by GH replacement, but baseline MetS status and obesity were strong predictors of MetS after GH treatment.

Friday, November 20, 2009

Researchers have identified an additional deleterious effect of glucocorticoid therapy in women treated for Cushing’s syndrome.

Duration of both endogenous hypercortisolism and more importantly exogenous glucocorticoid replacement therapy after successful surgery negatively affect bone mass," Maria-José Barahona, MD, of the department of endocrinology at the Hospital Mútua de Terrassa, told Endocrine Today.

Because patients in remission after successful treatment of Cushing’s syndrome often present with hypoadrenalism and require long-term glucocorticoid replacement therapy, researchers set out to assess whether glucocorticoid replacement had any further effect on bone after long-term remission of Cushing’s syndrome.

The study included 37 women at a mean age of 50 with cured Cushing’s syndrome (mean time of cure: 11 years), 14 women with active Cushing’s syndrome and 85 sex-, BMI- and age-matched controls.

Data indicated that women with cured and active Cushing’s syndrome who were estrogen sufficient had less bone mineral content, bone mineral density and osteocalcin when compared with the control group (P<.01). These differences were not observed in estrogen-deficient women.

"Duration of endogenous hypercortisolism and glucocorticoid replacement therapy required after successful surgery should be decreased as much as possible," Barahona said. "An early diagnosis of Cushing's syndrome and surgery, and regular assessment of the recovery of the adrenal axis function are highly recommended."

The duration of glucocorticoid replacement therapy was the main predictor for abnormal bone mineral content and BMD (P<.01).

"Bone mass and bone mineral density should be assessed at diagnosis of Cushing's syndrome and during follow-up. We suggest considering starting treatment with bisphosphonates as soon as low bone mass is confirmed, since a more rapid improvement in bone mass has been reported with alendronate in cured Cushing's syndrome.” - by Jennifer Southall

Familial Glucocorticoid Deficiency (FGD) is a rare autosomal recessive disease caused by ACTH resistance and leads to isolated glucocorticoid deficiency. Although FGD patients typically have normal mineralocorticoid secretion, subtle alterations in the renin-angiotensin-aldosterone axis have been reported in a subset of patients at presentation. Anecdotally some patients with FGD have been initially diagnosed as having AD, with implications for treatment and genetic counselling. Currently mutations in 3 genes: the ACTH receptor (MC2R); the melanocortin 2 receptor accessory protein (MRAP) and the Steroidogenic Acute Regulatory protein (StAR) are known to give rise to FGD types 1-3. We investigated a cohort of autoantibody-negative AD patients for mutations in these genes .

Methods

40 patients with known AD without evidence of autoimmune disease were screened for mutations in MC2R, MRAP and StAR . In addition patients were genotyped for the MC2R promoter polymorphism previously associated with reduced responsiveness to ACTH.

Results

No mutations in MC2R, MRAP or StAR were identified in any patient. The frequencies of the MC2R promoter polymorphism were similar to those reported in healthy controls.

Conclusions

FGD does not appear be underdiagnosed in the AD population. However, in ~50% of patients with FGD no genetic cause has yet been identified and it is possible that the other, as yet unidentified genes giving rise to FGD maybe implicated in AD.

Current evidence indicates a strong association between Cushing's syndrome, characterized by a cluster of systemic complications and increased cardiovascular risk. The biological link is cortisol overproduction, which influences various pathogenetic processes leading to cardiovascular damage, a main cause of increased mortality. Anthropometric and biochemical profile (including fasting glucose, lipids, potassium and coagulation parameters), clinical blood pressure measurement and electrocardiogram should be routinely carried out. Oral glucose tolerance test, 24-h ambulatory blood pressure monitoring, echocardiography and carotid ultrasound are recommended for further evaluation. Search for cardiac and vascular damage, according to specialist's advice, is mandatory in complicated hypertension or diabetes, as part of a comprehensive assessment. A combination of treatments directed against the aetiology of hypercortisolism and aimed at controlling cardiovascular risk factors, is required in this complex condition.

Document Type: Research article

DOI: 10.1111/j.1365-2265.2009.03610.x

Affiliations:1: Department of Medical and Surgical Sciences, University of Padova, Padova, Italy 2: Department of Statistical Sciences, University of Padova, Padova, Italy and Department of Psychiatry, State University of New York at Buffalo, NY, USA

Objective: Transsphenoidal surgery (TS) is the primary therapy for Cushing's disease (CD). The aims of this retrospective study were twofold: (i) investigate early and late results of TS for CD, and (ii) evaluate various postoperative tests in order to predict the outcome of TS.

* To whom correspondence should be addressed. E-mail: rizzoni@med.unibs.it.

Objective: Structural alterations of small resistance arteries in essential hypertensive patients (EH) are mostly characterized by inward eutrophic remodeling. However, we observed hypertrophic remodeling in patients with renovascular hypertension, in those with acromegaly, as well as in patients with non-insulin-dependent diabetes mellitus, suggesting a relevant effect of humoral growth factors on vascular structure, even independent from the hemodynamic load. Cortisol may stimulate the renin-angiotensin system and may induce cardiac hypertrophy. However, presently no data are available about small artery structure in patients with Cushing's syndrome.

Subjects: We have investigated the structure of sc small resistance arteries in 12 normotensive subjects (NT), in 12 EH subjects, and in eight patients with Cushing's syndrome (CS). Small arteries from sc fat were dissected and mounted on a micromyograph. The normalized internal diameter, media thickness, media to lumen ratio, and the media cross-sectional area were measured, as well as indices of oxidative stress.

Results: Demographic variables were similar in the three groups, except for clinic blood pressure. The media to lumen ratio was significantly greater in EH and CS, compared with NT; no difference was observed between EH and CS. The media cross-sectional area was significantly greater in CS compared with EH and with NT. An increased vascular oxidative stress was present in CS, as demonstrated by increased levels of superoxide anions, cyclooxygenase-1 and endothelial nitric oxide synthase in the microvessels.

Tuesday, November 10, 2009

The American Association of Clinical Endocrinologists (AACE) released new medical guidelines for the accurate diagnosis and effective ethical treatment of growth hormone deficiency in affected patients.

Growth hormone replacement therapy has proven useful for children and adults with scientifically proven growth hormone deficiency. In recent years, however, growth hormone use for anti-aging and athletic enhancement has increased to the point that this use currently accounts for approximately 30 percent of growth hormone prescriptions in the United States (1). A number of professional athletes have now admitted or have been alleged to have used HGH to speed recovery from injury or to enhance performance. Anti-aging centers tout benefits of HGH to slow the aging process.

"Although there is not a wealth of medical data published concerning HGH as a recovery tool for injured athletes, it's certainly not an approved indication for use," Dr. David Cook, Interim Division Chief of Endocrinology at the Oregon Health & Science University, and co-author of the new medical guidelines said.

In addition to addressing the increasing misuse of growth hormone in anti-aging and sports, the AACE guidelines more importantly address the accurate diagnosis and effective therapy for growth hormone deficient patients, as well as new cut points or benchmarks for growth hormone testing.

"These guidelines are the result of recent advancements in our understanding of the benefits of growth hormone replacement for patients," Dr. Cook said.

Responsiveness to growth hormone therapy is often determined by many variables, such as age, sex, adiposity, and concurrent medications. However, even after accounting for these variables, there remain highly individual differences in the response to growth hormone.

"Controlled trials, using strict dosing regimes and measuring clinical end points, such as body composition and insulin sensitivity, have shown us that growth hormone dosing should be individualized, with close attention to avoiding side effects," Dr. Cook said.

"If the cut point is five and the highest response is four, then the patient is growth hormone deficient," Dr. Cook said. "Some tests also depend upon body mass index such as the Arginine + growth hormone releasing hormone stimulation test."

Despite a growing body of evidence on the benefits of growth hormone therapy, there is still considerable inconsistency in the United States in the clinical practice of growth hormone replacement for adults.

"There are multiple factors accounting for this," Dr. Cook said. "Such as the high cost of growth hormone therapy, the need for daily injections, the lack of awareness regarding its indications, diagnosis, long-term surveillance, and concerns about whether there are long-term risks involved." Consequences of untreated growth hormone deficiency include cardiovascular complications, metabolic complications, osteopenia/osteoporosis, and diminished quality of life.

About AACEAACE is a professional medical organization with more than 6,000 members in the United States and 92 other countries. Founded in 1991, AACE is dedicated to the optimal care of patients with endocrine problems. AACE initiatives inform the public about endocrine disorders. AACE also conducts continuing education programs for clinical endocrinologists, physicians whose advanced, specialized training enables them to be experts in the care of endocrine disease, such as diabetes, thyroid disorders, growth hormone deficiency, osteoporosis, cholesterol disorders, hypertension and obesity.

About the American College of Endocrinology (ACE)The American College of Endocrinology (ACE) is the educational and scientific arm of the American Association of Clinical Endocrinologists (AACE). ACE is a scientific and charitable medical organization dedicated to promoting the art and science of clinical endocrinology for the improvement of patient care and public health. The American College of Endocrinology is the leader in advancing the care and prevention of endocrine and metabolic disorders by: providing professional education and reliable public health information; recognizing excellence in education, research and service; promoting clinical research; and defining the future of clinical endocrinology.

About Endocrine PracticeEndocrine Practice is the official scientific publication of the ACE and the AACE. It publishes the latest information in the treatment of diabetes, thyroid disease, obesity, growth hormone deficiency, sexual dysfunction, and osteoporosis, among others. The journal contains original articles, case reports, review articles, AACE Medical Guidelines for Clinical Practice, commentaries, editorials, and visual images. The total circulation of Endocrine Practice exceeds 5,300. Of these readers, 94 percent are physicians who treat endocrine-related disorders. Readership includes subscriptions in 84 countries, as well as many medical schools and research facilities. (1) Lyle WG. Human growth hormone and anti-aging. Plast Reconstr Surg. 2002;110:1585-1589.

Abstract

Multiple endocrine neoplasia syndrome 1 (MEN1) is a paracrine genetic autosomal dominant disease consisting of tumors in parathyroid, pancreas and pituitary glands. We report a case of a 44 year old male with MEN1 presenting insulinomas, parathyroid adenomas and a pituitary prolactin producing microadenoma.A 44 year old male presented to the emergency department with complaints of back pain. Initial imaging of the abdomen to rule out nephrolithiasis showed an 11cm mass at the head of the pancreas. On further questioning, the patient reported to have frequent symptoms suggestive of hypoglycemia for more than 20 years. Laboratory data on admission showed low glucose (46 mg/dl) and high calcium (12 mg/dl). A 72 hour fasting test confirmed the diagnosis of insulinoma. Hypercalcemia work-up revealed an elevated PTH (Calcium 12.6 mg/dl and PTH 200 pg/ml); a parathyroid scan showed multiple adenomas. A pituitary MRI did not reveal any tumors. However, labs were remarkable for decreased total testosterone (144 ng/dl), and elevated prolactin (104 ug/L). CT-guided biopsy of the mass at the head of the pancreas was consistent with a neuroendocrine tumor. The patient subsequently underwent resection of the pancreatic mass and parathyroidectomy. His hypercalcemia resolved after surgery and his hyperprolactinemia improved with dopamine agonist therapy. Unfortunately, his hypoglycemia did not resolve.We report the case of a 44 year old male patient with a new presentation of tumors of the parathyroid, pancreas and pituitary glands. Excellent history taking, further testing, and clinical suspicion lead to the diagnosis of MEN1 syndrome.

Case presentation

A 44 year old male presented to the Emergency Department complaining of severe left flank and back pain of approximately 1 month duration. Nephrolithiasis was suspected and further workup was performed. An abdominal CT scan failed to demonstrate renal calculi, but was remarkable for an 11 centimeter mass at the head of the pancreas, a 2 centimeter mass at the tail of the pancreas, and portal hepatic lymph nodes (figure 1). The patient was admitted for further evaluation of these abdominal masses. Initial laboratory data noted hypoglycemia (glucose of 46 mg/dL) and hypercalcemia (calcium of 12 mg/dL).

On further questioning, the patient reported to have frequent episodes of dizziness and sweating for more than 20 years. He had grown accustomed to these spells and would often ingest candy to prevent or resolve the symptoms. He had never before sought medical attention for these episodes. He denied any previous diagnosis of diabetes, use of insulin, oral hypoglycemics, herbal remedies or other prescription medications. He also reported decreased libido for the past few years. Physical exam revealed a well-nourished, obese male in no distress. Vital signs were stable. His skin exam was remarkable for acanthosis nigricans, and no masses were palpable on abdominal examination. The rest of his physical exam was within normal limits. His family history was remarkable for type 2 diabetes in his mother and colon cancer in his aunt.

A hypercalcemia work-up was also pursued, revealing both elevated calcium (12.6 mg/dl) and PTH (200 pg/ml) levels. A parathyroid scan revealed intense radiotracer activity in the upper and lower left poles, suggestive of adenomas. To evaluate for pituitary involvement, pituitary imaging and anterior pituitary hormone levels were obtained. The pituitary MRI did not reveal any tumors. However, findings of decreased total testosterone (144 ng/dl) and elevated prolactin (104 ug/L), were indicative of a microprolactinoma. The remainder of the anterior pituitary function was normal.

CT-guided biopsy of the mass at the head of the pancreas was consistent with a neuroendocrine tumor. The patient subsequently underwent a modified Whipple procedure to resect the 11 centimeter mass in the pancreatic head and a three and one half gland parathyroidectomy. His hypercalcemia resolved after surgery and his hyperprolactinemia improved with dopamine agonist therapy. His back pain, which was likely secondary to compression of the celiac plexus from the pancreatic mass, improved after surgery. Unfortunately, his hypoglycemia did not resolve.

Genetic screening for MEN1 was positive, showing a known mutation in the MEN1 gene. The patient continues to receive medical treatment, and his children have been referred for genetic counseling.

Review of literature

MEN1 syndrome is a rare genetic autosomal dominant disease, with an incidence of 2 in 100000 (1, 2). It consists of tumors of three glands; parathyroid, pancreas, and anterior pituitary (3). At least two gland involvement is required to make the diagnosis. The disease originates from mutations of the MEN1 gene, which codes for the menin protein found on chromosome 11q13 (4, 5). The function of this protein is not fully understood but is thought to be important for tumor suppression. Patients with MEN1 usually present with detectable gene mutations (up to 75% of cases) (3). Failure of detection of this mutation in MEN1 kindred does not rule out the possibility carrier status, but reflects mutations located at unrecognized sites of the gene (3, 6). There is currently little evidence that early screening of asymptomatic family members will reduce morbidity or mortality in MEN1 (6). However, if one decides to screen family members of affected individuals, measurement of serum calcium is the most cost-effective approach (6).

Hyperparathyroidism is the most common finding in MEN1 patients and presents with over 90% penetrance by the age of 50 (1, 7). Hyperparathyroidism in MEN1 is usually associated with multiple adenomas, which is consistent with our patient’s findings. Treatment for hyperparathyroidism is aggressive surgical resection. Indications for surgery include symptomatic or marked hypercalcemia, nephrolithiasis, or diminished bone density (7). Surgery however, is also considered an acceptable alternative for patients with asymptomatic hypercalcemia in MEN1 (1). Initial surgery often involves three and one-half gland removal and occasionally thymectomy to resect possible intrathymic parathyroid glands (8). Recurrence is common and is as high as 30% (2, 8).

The second most common finding in MEN1 patients, comprising almost 70% of the cases, are enteropancreatic tumors (1, 3). The most common type of tumor is a gastrinoma (Zollinger Ellison Syndrome). Patients with MEN1 and Zollinger Ellison Syndrome have higher incidence of esophageal stricture, Barrett’s esophagus and dysplasia when compared to patients with only Zollinger Ellison Syndrome (11). Insulinomas, as our patient had, are usually small, multiple and are less common. The diagnosis of insulinoma depends upon the documentation of symptomatic hypoglycemia that is reversed by the administration of glucose. These findings should be accompanied with inappropriately normal or elevated serum insulin concentrations (9). The preferred treatment for insulinoma is surgery. However, treatment is complicated by the possible presence of multiple small insulinomas and continuing risk of persistent hypoglycemia even after surgery (1, 9). Therefore, it is recommended that patients undergo excision of tumors at the head of the pancreas as well as a distal sub-total pancreatectomy (9). In our case, removal of the mass at the head of the pancreas did not resolve the hypoglycemia. The other pancreatic masses were not resected during the initial procedure due to concern for intraoperative complications. Re-exploration was discussed with the patient, but he has refused further surgery at this time.

Approximately 15-20% of MEN1 patients have clinically apparent pituitary tumors (3). MEN1 pituitary tumors share the same clinical profile as sporadic tumors (2). The most common is a prolactinoma, but GH-secreting, ACTH-secreting, and non-secreting tumors can occur (3, 10). Our patient had typical laboratory and imaging findings consistent with a microprolactinoma. Treatment for prolactinomas in MEN1 should be no different as of isolated prolactinomas; initial medical therapy with dopamine agonists is the treatment of choice (1). If treatment is successful, it is important to continue regular biochemical evaluation of the pituitary for possible recurrence (3).

We report the case of a 44 year old male patient with a presentation of a very rare disease, MEN1 syndrome. He had evidence of tumors of the parathyroid, pancreas and pituitary glands. Usually MEN1 patients are first diagnosed when they present with hypercalcemia. Our patient’s diagnosis was made only after he presented with back and flank pain, and imaging of his abdomen incidentally noted multiple abdominal tumors. Careful history taking, clinical suspicion, and further testing led to making an important diagnosis. This case is a good reminder of how a patient can present with common symptoms, but may in fact have a very unusual and uncommon disease underlying the condition.

Kim Yaman works two jobs to help pay for her mounting health care costs. Yaman has Cushing's Disease, a rare tumor of the pituitary gland.

BY SARAH AVERY - Staff Writer

Galvanized by the difficulties a Cary woman has had paying medical bills despite two jobs and health insurance, a group of more than 60 community activists gathered in Raleigh on Saturday to raise support for a health care reform bill.

The group, all friends of Cary grandmother Kim Yaman, fanned out from downtown Raleigh to knock on doors and give out information about bills being considered in Washington.

Yaman, whose story was featured last month in The News & Observer as part of a series about health care reform, has Cushing's Disease, a rare tumor of the pituitary gland. The illness causes weight gain, muscle weakness, high blood pressure and bone loss, among other problems.

For years, Yaman didn't know what was causing her ill health, but frequent visits to doctors and myriad tests caused escalating medical bills. She took on a second job at the Galaxy Theater in Cary to augment her pay at the Wake County Public School System, but the expenses still mounted, despite insurance.

Last month, Yaman held a demonstration at Sen. Kay Hagan's office to call for health reform that includes a public option. Yaman and friends handed out Moon Pies to passers-by, because they said they weren't asking for the moon in seeking reform.

Saturday's event drew community activists from Seattle, California, New York and Chicago - all who had worked with Yaman last year during the presidential campaigns and were eager to help a cause they hoped would help their friend.

Tuesday, November 3, 2009

Today is the twenty-second anniversary of my pituitary Cushing's surgery. It seems like I should be feeling better by now, right?

Sure, some things are better although I'm hard-pressed to say which.

My endo says I don't have Cushing's anymore, so that's a good thing.

I do have a growth hormone deficiency, I'm panhypopituitary and have adrenal insufficiency. Kinda like the old jumping out of the frying pan into the fire.

One thing cured, 3 others added. Hmmm - I'm not sure I like the math.

Supposedly, I have a slightly longer life expectancy because the tumor is gone...but the GH deficiency can take away up to 5 years, the kidney cancer can take away more so I'm losing ground on that, too.

Because of the cancer, I can't do anything about the GH deficiency. Because of the treatment for the GH deficiency, I might have gotten the cancer in the first place. Catch 22. Interesting that this phrase coincides with the anniversary number.

Then, I often wonder - is life expectancy only about years? What if there's no quality?

I found this article especially interesting. This question was asked of a group of endos at an NIH conference a few years ago - if you saw someone on the street who looked like they had symptoms of fill-in-the disease, would you suggest that they see a doctor. The general answer was no. No surprise there.

Patients, if you see someone who looks like s/he has Cushing's, give them a discrete card.

Spread The Word! Cushing's Pocket Reference

Robin Writes:

This has been a concern of mine for some time. Your post spurred me on to do something I've been meaning to do. I've designed something you can print that will fit on the business cards you can buy just about anywhere (Wal-mart included). You can also print on stiff paper and cut with a paper cutter or scissors. I've done a front and a back.

A Spanish woman of 55, Montse Ventura, recently met the woman she refers to as her "guardian angel" on a bus in Barcelona. The stranger – an endocrinologist – urged Ventura to have tests for acromegaly, a rare disorder involving an excesss of growth hormone, caused by a pituitary gland tumour. How had the doctor made this unsolicited diagnosis on public transport? Apparently the unusual, spade-like shape of Ventura's hands was a dead giveaway.

But how many off-duty doctors would feel compelled to alert strangers to symptoms they spot? "If I was sitting next to someone on a bus with a melanoma, I'd say something or I wouldn't sleep at night," says GP Mary McCullins. "We all have a different threshold for interfering and you don't want to terrify people, but this is the one thing I'd urge a total stranger to see a doctor about." So what other symptoms might prompt a doctor to approach someone on the street?

Moon face

Cushing's syndrome is another rare hormone disorder which can be caused by a non-cancerous tumour in the pituitary gland. "A puffy, rounded 'moon face' is one of the classic signs of Cushing's," says Dr Steve Field, chair of the Royal College of GPs. "In a social situation, I wouldn't just say, 'You're dangerously ill' but I'd try to elicit information and encourage them to see a doctor."

Different-sized pupils

When one pupil is smaller than the other, perhaps with a drooping eyelid, it could be Horner's syndrome, a condition caused when a lung tumour begins eating into the nerves in the neck. This can be the first obvious sign of the cancer. "I'd encourage someone to get this checked out," says Dr Simon Smith, consultant in emergency medicine at the Oxford Radcliffe Hospitals Trust. "People often have an inkling that something's wrong, and you might spur them to get help sooner."

Clubbing fingers

Some people are born with club-shaped fingers, but if, over time, they become "drumstick-like", this could signify serious problems such as lung tumours, chronic lung infections or congenital heart disease. "Because it happens gradually, some people disregard clubbing," says Smith. "But I'd say something because it can be an important symptom in many serious illnesses."

Lumpy eyelids

Whitish yellowy lumps around the eyelids can be a sign of high cholesterol, a major factor in heart disease. Sometimes you also get a yellow circle around the iris. "I would suggest they got a cholesterol test with these symptoms," says Smith. "They can do something about it that could save their life."

Suntan in unlikely places

A person with Addison's disease, a rare but chronic condition brought about by the failure of the adrenal glands, may develop what looks like a deep tan, even in non sun-exposed areas such as the palms. Other symptoms (tiredness, dizziness) can be non-specific so the condition is often advanced by the time it is diagnosed. Addison's is treatable with lifelong steroid replacement therapy. "If someone was saying they hadn't been in the sun but had developed a tan, alarm bells would ring and I'd probably ask how they were feeling," says McCullins.

Trench mouth

Putrid smelling breath – even if the teeth look perfect – can be a sign of acute necrotising periodontitis. "I'd be able to tell when someone walks through the door," says dentist Laurie Powell. "But people become accustomed to it and don't notice." Untreated, the condition damages the bones and connective tissue in the jaw. It can also be a sign of other diseases such as diabetes or Aids.

About Me

I am a Cushing's patient who has dealt with Cushing's symptoms since 1983 (or earlier) and the aftereffects of pituitary surgery since 1987.

Because I had very little support for my symptoms, diagnosis and surgery, I decided to try to make things a little better for other patients and started a support site called Cushing's Help and Support in 2000. The site has grown to astronomical numbers. This disease isn't as rare as doctors have told us!

In 2006, I was also diagnosed with kidney cancer (renal cell carcinoma). My left kidney and adrenal gland were removed. Having an adrenal gland removed complicates my post-Cushing's symptoms.